Anticoagulant Classes, Indications, Contraindications, and Half-Lives
Anticoagulants are divided into three major classes: vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs), and parenteral anticoagulants (heparins and factor Xa inhibitors), each with distinct pharmacologic properties, clinical indications, and safety profiles that guide their use in preventing and treating thromboembolism.
Classes and Pharmacologic Properties
Vitamin K Antagonists (VKAs)
- Agent: Warfarin
- Mechanism: Inhibits vitamin K-dependent clotting factors (II, VII, IX, X)
- Half-life: Variable, typically 36-42 hours
- Onset: Requires minimum 5 days overlap with parenteral anticoagulation 1
- Monitoring: Requires regular INR monitoring, target 2-3 for most indications 2
Direct Oral Anticoagulants (DOACs) 3, 4
Direct Thrombin Inhibitor:
- Dabigatran:
Factor Xa Inhibitors:
Rivaroxaban:
Apixaban:
Edoxaban:
Parenteral Anticoagulants
Unfractionated Heparin (UFH):
Low Molecular Weight Heparin (LMWH):
- Half-life: 3-6 hours (subcutaneous) 10
- Partial reversal: Protamine sulfate
- Monitoring: Anti-Xa levels (not routine)
Fondaparinux:
- Half-life: 17 hours 11
- No reversal agent available
- Monitoring: Anti-Xa levels
Direct Thrombin Inhibitors (Parenteral):
- Argatroban: Half-life 45 minutes, hepatic metabolism 10
- Bivalirudin: Half-life 25 minutes, enzymatic elimination 10
- Lepirudin: Half-life variable, renal elimination 10
Clinical Indications
Atrial Fibrillation (Stroke Prevention) 4
First-line agents: DOACs (dabigatran 150mg BID, apixaban 5mg BID, rivaroxaban 20mg daily, edoxaban) 4
- Dabigatran 150mg BID: Class I, Level B evidence 4
- Apixaban 5mg BID: Class I, Level B evidence 4
- Rivaroxaban 20mg daily: Class IIa, Level B evidence 4
- Warfarin: Class I, Level A evidence 4
Mandatory warfarin use:
Venous Thromboembolism (VTE)
Acute Treatment:
- DOACs are first-line for eligible patients 7
- Select low-risk patients can initiate DOAC therapy outpatient 7
Cancer-Associated VTE:
- LMWH is preferred for initial 5-10 days and long-term therapy (at least 6 months) 2
- LMWH demonstrated 49% relative risk reduction vs warfarin in cancer patients 2
- Consider indefinite anticoagulation for active cancer (metastatic disease, ongoing chemotherapy) 2
VTE Prophylaxis:
- Major abdominal/pelvic cancer surgery: LMWH or UFH for duration of hospitalization 2
- Extended prophylaxis (up to 4 weeks) for high-risk features: obesity, residual malignancy, prior VTE history 2
High Thrombotic Risk Conditions 9
Mechanical valve prosthesis: Warfarin only (mitral > aortic risk) Recent VTE (within 3 months): Any oral anticoagulant Left ventricular thrombus: Warfarin only Left atrial appendage thrombus: Warfarin only Recurrent unprovoked VTE: Long-term anticoagulation
Contraindications
Absolute Contraindications 2
- Active, uncontrollable bleeding
- Active cerebrovascular hemorrhage
- Dissecting or cerebral aneurysm
- Bacterial endocarditis
- Severe uncontrolled malignant hypertension
- Severe head trauma
Relative Contraindications 2
- Pericarditis
- Active peptic or GI ulceration
- Pregnancy (warfarin specifically)
- Heparin-induced thrombocytopenia (for heparin, LMWH)
- Epidural catheter placement
Renal Impairment Considerations 4, 5
Dabigatran: Contraindicated if CrCl <30 mL/min; dose reduction to 75mg BID if CrCl 15-30 mL/min 4 Rivaroxaban: Caution with severe renal insufficiency (CrCl <15 mL/min) 6 Apixaban: Least affected by renal impairment (25% renal elimination) 5 Edoxaban: Caution with severe renal insufficiency 6
Critical Management Considerations
Bleeding Management 9, 1
Major bleeding on warfarin:
- Vitamin K 10mg IV (slow infusion to avoid anaphylaxis) 1
- 4-factor prothrombin complex concentrate (PCC) preferred over FFP 1, 7
- PCC more rapid reversal than FFP (4.8h vs 7.3h to normalize INR) 1
Major bleeding on DOACs:
- Dabigatran: Idarucizumab (specific reversal) 7
- Rivaroxaban/Apixaban: Andexanet alfa (specific reversal) 7
- If reversal agents unavailable: 4-factor PCC or activated PCC 9
- Activated charcoal if <3 hours since last dose 6
- Do NOT use platelet transfusion or desmopressin (no evidence, potential harm) 6
Perioperative Management 11
DOAC interruption timing:
- Last dose at D-5 or plasma concentration <30 ng/mL for neuraxial procedures 11
- No bridging with LMWH required 12
Parenteral anticoagulant interruption:
- Argatroban: Stop 4 hours before surgery 11
- Bivalirudin: Stop 2 hours before surgery 11
- Fondaparinux: Last injection >36 hours before surgery 11
- Danaparoid: Stop >36 hours before surgery 11
Resumption after bleeding:
- High thrombotic risk: Unfractionated heparin IV infusion within 1-3 days (short half-life, reversible) 9
- Prophylactic doses initially to balance bleeding/thrombotic risk 9
Special Populations
Heparin-Induced Thrombocytopenia (HIT):
- Use non-heparin anticoagulants: argatroban, bivalirudin, fondaparinux, or danaparoid 11, 10
- Fondaparinux acceptable option despite off-label use 11
- Avoid all heparin products including LMWH 11
Pregnancy:
Common Pitfalls
- DOAC adherence: Short half-lives mean missed doses rapidly lose anticoagulant effect 4
- Warfarin-argatroban transition: Argatroban prolongs INR; measure INR after stopping argatroban several hours or use chromogenic factor X assay 10
- Laboratory monitoring: Standard PT/aPTT unreliable for DOACs; use specific anti-Xa or anti-IIa assays if needed 6
- Renal function: Critical for dabigatran dosing (80% renal elimination) 5
- Cancer patients: LMWH superior to warfarin for VTE treatment; DOACs emerging as alternative 2